NOTES
5782
Acknowledgment.-The authors wish to thank Prof. F. Bergmann for spectroscopic data. 1)hPARTMENT O F ORGANIC CHEIvIIbrRY THEHEBREW UNIVERSITY JERUSALEM, ISRAEL -. ._ _ --
The Use of Dimethylformamide in the Ullmann Reaction BY ~ ~ A T H AKORNBLCM N A N D DAVIDL. KENDALL~ RECEIVEDJ U N E 27, 1952
LVhen a relatively reactive aryl halide is heated with copper powder in the absence of a solvent a vigorous, exothermic reaction may occur. In niany instances it has, therefore, proved advantageous to add a diluent and for this purpose nitrobenzene has most often been used, although toluene, p-cymene, naphthalene, biphenyl and anthracene have also been employed.2
VOl. 74
Experimental Thc copper powder used was Natural Copper 44F (United States Bronze Powder Works) pretreated according to Kleiderer and Adams.' Dimethylformamide6 (du Pont) was stored over calcium hydride at least 12 hours; very possibly no drying is necessary but this point was not investigated. The 2-chloro-3-mcthoxynitrobenzene (m.p. 94") was prepared according to Finger .6 o-Chloronitrobenzene was obtained from Monsanto and the other starting halidcs were Eastman Kodak Co. "white label" products. The following preparation of 2,2'-dimethoxy-6,6'-dinitrobiphenyl is typical. In the other runs the only changes were in the time of reaction (6. Table I ) and the solvent used for recrystallizing the product. With a given biaryl the same solvent was employed as had been used by the workers cited in Tablc I. Preparation of 2,2'-Dimethoxy-6,6'-dinitrobipheny1.Twenty grams of 2-chloro-3-methoxynitrobenzene and 100 ml. of dirnethylformamide were placed in a 200-ml., 3-neck flask equipped with reflux condenser and a tantalum Hershberg-type stirrer. The solution was heated to reflux and then 20 g. of copper powder was added in one portion. Iicating a t reflux was continued for four hours after which anothcr 20-g. portion of copper powder was added; reflux-
TABLE I PREPARATION OF BIARYLS
Halide
Biaryl
Rcaction time, hr.
Yield, hl.p., OC.0
%* 8JC
Previous yield, %
2-Chloro-3-methoxynitrobenzene 2,2'-Diniethoxy-6,6'-dinitrobiphetiyl 8 231-232 iod o- Chloronitrobenzene 2,2'-Dinitrobiphenyl 125.5-126 52-43le 8 80 2,5-Dichloronitrobenzeiic 4,4'-Dichloro-2,2'-dinitrobiphenyl 421 138-139 8 75 P m-Iodotoluene 3,3'-Dimethylbiphenyl 72 3jh 55 4,4'-Dimethylbiphenyl 72 p- Iodotoluene 122-122.5 54' 68 24 Methyl p-iodobenzoate 4.4 '-Dicarbomethoxybiphenyl 2 12-2 14 74' 70k Methyl m-iodobenzoate 3,3'-Dicarbomethoxybiphenyl 72 103-104 GO1 89 p-Iodophenetole 4,4'-Diethoxybiphenyl 72 176-177 72" 77 or-Iodonaphthalerie 24 1,I '-Binaphthyl 159-159.5 68" 76 All m.ps. determined on a Fisher-Johns hot-stage. * These are the yields of products which have been recrystallized to the melting points given in this Table. Average of four runs. R. A d a m and G. C. Finger [THISJOURNAL, 61, 2828 (1939)l; m.p. 226-228" (uncor.). R. C. Fuson and E. A. Cleveland [Org. Syntheses, 20, 45 (1940)l; m.p. 123.5-124.5' F. Ullmann and J. Bielecki [Ber.,34, 2174 (1901)]; m.p. 136". (cor.). B.p. 135' at 3 mm., %*OD 1.5925; 0. S . Mills [IVature, 167, 726 (1951)l reports b.p. 130' a t 1 mm., n m 1.5962; ~ N.Kornblum [Org. Syntheses, 21, 30,(1941)] gives b.p. 115" at 3 mm., x Z o1.5945. ~ F. Ullmann [Ann., 332, 38 (1904)l. I?. Ullmann, ibid.; m.p. 122". 1 When account is taken of the starting material which is recovered the yield rises t o 93%; presumably a longer reaction time would be beneF. Ullmann, ibid.; m.p. 214". I F. Ullmann, ibid.; m.p. 104". F. Ullmann, ibid.; m.p. 178". I(. Brass ficial. and R. Patzelt [Ber., 70, 1349 (1937)l; m.p. 154'. C. Willgerodt and P. Schlosser [Ber., 33,698 (1900)], report m.p. 160.5' (cor.).
Incidental to another investigation, it has now been found that dimethylformamide is a good solvent for the Ullmann reaction, in spite of the fact that its boiling point, 133', is lower than that of most of the diluents previously used. Among other things, dimethylformamide has the considerable advantage over the previously employed diluents of being water soluble; hence it can easily be removed from the reaction product. Not only does this simplify the isolation procedure but, as can be seen from Table I, the yields are significantly higher than those obtained previously. It should be emphasized that with those halides which are inert under the usual Ullmann conditions the present procedure offers no advantage. Thus, after 24 hours in refluxing dimethylformamide the following halides had undergone little or no reaction with copper powder : p-bromophenetole, m-chloronitrobenzene, p-chloronitrobenzene, p-brom~nitrobenzene~ and a-bromonaphthalene. (1) Atomic Energy Commission Predoctoral Fellow 1950-1952. ( 3 ) P. E. Fanta, Chem. R e v s , 38, 149 (1946).
(3) W. Davey and
la. W.Latter
( J . Chem. Suc., 264 (1948)) ob-
ing was continued for a second four-hour period. On cooling, the reaction mixture was poured into two liters of water and then filtered. The solids were extracted with a total of two liters of boiling acetone. Concentration of the acetone extracts gave 11.1 g. of yellow crystals melting a t 231232' (uncor.); further evaporation of the acetone, followed by the addition of absolute ethanol, gave another 2.8 g., m.p. 228-229'. The 2.8 g. was digested for 10 minutes on the steam-bath with about 5 ml. of glacial acetic acid. After cooling t o room temperature the crystals were isolated by filtration and then washed with a little glacial acetic acid. I n this way a small amount of copper salts was removed leaving 2.4 g. of the dimethoxydinitrobiphenyl, 1n.p. 231-232" (uncor.), total yield 13.5 g. (84%). DEPARTMENT OF CHEMISTRY PURDUE UNIVERSITY INDIANA LAFAYETTE, tained no dinitrobiphenyl on treating m- or p-chloronitrobenzene with copper powder either in t h e absence of solvent (at ZOO-220") or in retluxing nitrobenzene. With p-bromonitrobenzene a 15% yield of 4,4'-dinitrobiphenyl was obtained after nine hours in reEuxing nitrobenzene. In the absence of a solvent p-brornonitrobenzene gave the biaryl in 3 G % yield after 40 minutes a t 200-220'. (4) E. C . Kleiderer and R . Adams, THISJOURNAL, 66, 4219 (1933). (): We wish to thank t h e Grasselli Division of E. I. du Pont de Nemours & Co., Inc., for a generous supply of dimethylformamide. ( 6 ) G. C. Finger, Ph.D. Thesis, University of Illinois, 1938, p. 56.
